The ultimate goal of the CDA-2 is for Dr. Montalvo-Ortiz to obtain training in advanced methods of statistical genetics, functional genomics and bioinformatics to identify molecular biomarkers of posttraumatic stress disorder (PTSD) that can help monitor the progression of PTSD and inform prevention efforts and personalized care for U.S. veterans. To accomplish this goal, she will investigate the epigenomics and transcriptomics of PTSD in veterans using an integrative multi-omics approach. This study is innovative because it represents the largest longitudinal study, to date, of the epigenomics of PTSD in U.S. veterans, will address the causality of the epigenetic biomarkers identified, and will use cutting-edge bioinformatic methods to prioritize biomarkers for PTSD by integrating different datasets. This study will leverage current knowledge and provide novel insights on the etiology of PTSD needed to improve the healthcare for U.S. veterans that suffer from this disorder. The proposed research and training plans are highly complementary; Dr. Montalvo-Ortiz will acquire crucial new knowledge and skillsets that will advance her work to include 1) longitudinal analysis of genome-wide DNA methylation data; 2) RNA-sequencing analysis; 3) integration of multi- omics (DNA methylation-gene expression) datasets; and 4) functional genomics analysis using existing and novel bioinformatics tools. This CDA-2 grant will augment her neuroscience training and initial exposure in the study of the effects of trauma in psychiatric disorders with advanced and cutting-edge skills in psychiatric genomics and bioinformatics. Her mentorship is composed by a multidisciplinary group of established field-leading researchers at VA CT Healthcare and Yale. The innovative research and the supportive and collaborative environment of these institutions will equip her well in developing into an independent VA researcher with the tools necessary to conduct rigorous integrative multi-omics research on some of the most prevalent and disabling psychiatric disorders in U.S. veterans. ! !